ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.441+1G>C (rs62517166)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000672959 SCV001370851 pathogenic Phenylketonuria 2020-04-05 reviewed by expert panel curation The c.441+1G>C variant in PAH is a canonical splice-site variant predicted to result in skipping of exon 5, leading to a frameshift, premature protein truncation, and NMD (PVS1). It is present at an extremely low frequency in gnomAD (MAF = 0.00000398, less than the 0.0002 MAF cutoff) (PM2) and absent from other ethnically diverse control databases, including 1000 Genomes and ESP (PM2). It is reported Likely Pathogenic in Clinvar (Variation ID 556894) by one diagnostic testing lab. It has been reported in the published literature in a Kurdish patient with classic PKU (PMID: 24048906), diagnosed by plasma Phe levels; BH4 deficiency was excluded by urinary pterin analysis (PP4_Moderate). The patient was homozygous for the variant (PMID: 24048906) (PM3_Supporting). Classification: Pathogenic Supporting Criteria: PVS1, PM2, PM3_Supporting, PP4_Moderate
Counsyl RCV000672959 SCV000798119 likely pathogenic Phenylketonuria 2018-02-26 criteria provided, single submitter clinical testing

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